Significance: The k _cat values of enzymes are important for the study of metabolic systems. However, the current use of k _cat presents major difficulties, as values for most enzymes have not been experimentally measured, and experimentally available values are often measured under nonphysiological conditions, thereby casting doubt on the relevance of k _cat under in vivo conditions. We present an approach that utilizes omics data to quantitatively analyze the relationship between in vitro k _cat values and the maximal catalytic rate of enzymes in vivo. Our approach offers a high-throughput method to obtain enzyme kinetic constants, which reflect in vivo conditions, and are useful for more accurate and complete cellular metabolic models.

Background: Since the beginning of the Sever Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, school closure as a mitigating measure was at the center of a public and professional debate. While the negative effects of school closure cannot be ignored, accumulating data suggested that it is necessary for reducing community transmission. Our study presents an optional strategy for safe school opening during a pandemic, implemented in selected Israeli high schools by a special task force constructed by the Sheba Medical Center (SMC). Methods: The study took place between November 2020 and April 2021. Three schools from different areas of Israel were enrolled. The participants were asked to undergo bi-weekly SARS-CoV-2 rapid diagnostic antigen tests (Ag-RDT). Those who tested positive were requested to self-isolate, whereas their school contacts were tested daily by Ag-RDT. Participants with a previously documented SARS-CoV-2 infection or who were found to be SARS-CoV-2 seropositive upon enrollment were exempted from screening. Results: Of a total of 361 participants who enrolled in the study, 12.3% were found to be seropositive. Fourteen SARS-CoV-2 cases were detected (3.5%), 12 of them in one single school located in an endemic area for SARS-CoV-2. The 14 cases resulted in 84 days of COVID-19-related absence from school, comparing with 1775 potential days of COVID-19-related absence under a strategy implementing self-isolation instead of testing. Conclusions: Safe continuation of academic routine during the pandemic is possible when using rapid Ag-RDT as a screening tool, while allowing swab collection by trained students and teachers.

Up until now, there is much debate about the role of asymptomatic patients and pauci-symptomatic patients in severe acute respiratory syndrome novel coronavirus 2 (SARS-CoV-2) transmission, and little is known about the kinetics of viral ribonucleic acid (RNA) shedding in these populations. This article aims to describe key features and the nature of asymptomatic and pauci-symptomatic SARS-CoV-2 infected patients. The cohort consisted of six participants, three pairs, which were infected with SARS-CoV-2 during February 2020 on board the Diamond Princess. Of the six confirmed (reverse transcription polymerase chain reaction [RT-PCR]) cases, four were initially diagnosed in Japan and two upon their arrival to Israel. Duration of infection was between four days and up to 26 days. Of the six patients, three were completely asymptomatic and the others were pauci-symptomatic. All five patients in whom a computerized tomography (CT) scan was performed had lung pathology. In one patient, infectivity was tested using cell culture and a cytopathic effect was demonstrated. A serology test was performed in three of the patients and all three had a positive immunoglobulin G (IgG) four to eight weeks after disease onset. This case series demonstrates that asymptomatic and pauci-symptomatic patients may play a role in infection transmission by demonstrating probable transmission among asymptomatic spouses and by demonstrating a viable virus via a cell culture. Additionally, asymptomatic and pauci-symptomatic patients can have lung pathology and developing IgG antibodies.

Nosocomial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks among health care workers have been scarcely reported so far. This report presents the results of an epidemiologic and molecular investigation of a SARS-CoV-2 outbreak among laundromat facility workers in a large tertiary centre in Israel. Following the first three reported cases of SARS-CoV-2 among laundromat workers, all 49 laundromat personnel were screened by qRT-PCR tests using naso- and oropharingeal swabs. Epidemiologic investigations included questionnaires, interviews and observations of the laundromat facility. Eleven viral RNA samples were then sequenced, and a phylogenetic analysis was performed using MEGAX. The integrated investigation defined three genetic clusters and helped identify the index cases and the assumed routes of transmission. It was then deduced that shared commute and public showers played a role in SARS-CoV-2 transmission in this outbreak, in addition to improper PPE use and social gatherings (such as social eating and drinking). In this study, we present an integrated epidemiologic and molecular investigation may help detect the routes of SARS-CoV-2 transmission, emphasising such routes that are less frequently discussed. Our work reinforces the notion that person-to-person transmission is more likely to cause infections than environmental contamination (e.g. from handling dirty laundry).

Background: Unfortunately, the majority of patients with colorectal cancer liver metastases (CRCLM) experience disease recurrence following hepatic surgery. The key challenge is therefore optimal patient selection, which currently relies on anatomical and clinical parameters. Exploring a potential molecular signature may be predictive for seeing a clinical benefit from CRCLM resection. Methods: Consecutive patients who underwent CRCLM resection at our medical center between 2006 and 2016 were divided into cohorts of “good prognosis” (GP) or “poor prognosis” (PP) based on the time interval between their resection and disease recurrence. Proteomic analysis was performed on the surgical specimen and correlation analysis was carried out with demographics and clinical outcomes. Results: Proteomic analysis revealed 99 differentially expressed proteins of which a third were associated with extracellular matrix (ECM) pathways as the matrix metalloproteinases (MMPs). Multivariate analysis yielded a statistically differential proteomic pattern between the cohort regardless of perioperative treatment. Conclusion: Our results indicate a different proteomic landscape in the cohort of patients who had a clinical benefit from CRCLM resection which appears to be correlated with ECM pathways. Further prospective studies are needed to define the role of ECM pathways in prognostics and patient selection for surgical procedures for CRCLM.